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We established a murine IE model in C57BL6 mice in which aortic valve injury was induced via wire-injury and followed by intravenous injection of Staphylococcus aureus. Infection was confirmed by blood and valve cultures, and cardiac function was evaluated by echocardiography. Systemic cytokine levels were measured, and immune cell infiltration in valve tissue was assessed by flow cytometry and immunofluorescence. In the murine model, IE was induced in 77\/85 animals. Male mice exhibited significantly higher bacterial loads in blood and valves, greater valve cusp enlargement, increased ventricular volumes, and more frequent aortic regurgitation. Both sexes showed strong neutrophilic responses, but males had markedly elevated systemic IL-1\u03b1, IL-1\u03b2, IL-6, and TNF-\u03b1 levels. Females demonstrated earlier and more robust recruitment of CD68\u207a and CD206\u207a macrophages, as well as Ly6G\u207a neutrophils, to the injured valve, correlating with reduced bacterial vegetations. This murine model mirrors the clinical sex disparity in IE: males develop more severe disease and systemic inflammation, while females benefit from a rapid, localized immune response. These findings provide a platform for dissecting molecular drivers of sex-specific susceptibility in IE.<\/jats:p>","DOI":"10.1007\/s00395-025-01127-8","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T16:38:04Z","timestamp":1754498284000},"page":"1027-1035","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex differences in a murine model of infective endocarditis"],"prefix":"10.1007","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3126-221X","authenticated-orcid":false,"given":"Benedikt","family":"Bartsch","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ra\u00fal Nicolas","family":"Jamin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axel","family":"Schott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muntadher","family":"Al Zaidi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikola","family":"L\u00fcbbering","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah","family":"Billig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Kurts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg","family":"Nickenig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marijo","family":"Parcina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Zimmer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina Katharina","family":"Weisheit","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"key":"1127_CR1","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1161\/CIRCULATIONAHA.121.054108","volume":"145","author":"BA Aguado","year":"2022","unstructured":"Aguado BA, Walker CJ, Grim JC, Schroeder ME, Batan D, Vogt BJ, Rodriguez AG, Schwisow JA, Moulton KS, Weiss RM (2022) Genes that escape X chromosome inactivation modulate sex differences in valve myofibroblasts. 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